Development of therapeutic and prophylactic vaccine against Tuberculosis using monkey and transgenic mice models

Kita, Yoko; Okada, Masaji; Nakajima, Takeshi; Kanamaru, Noriko; Hashimoto, Satomi; Nagasawa, T; Kaneda, Yasufumi; Yoshida, Shigeto; Nishida, Yasuko; Nakatani, Hitoshi; Takao, Katsuyuki; Kishigami, Chie; Nishimatsu, Shiho; Sekine, Yoshihiro; Takamori, Yasushi; McMurray, David N.; Cruz, E C De la; Tan, Esterlina V.; Abalos, Rodolfo M.; Burgos, Jasmin; Saunderson, Paul; Sakatani, Mitsunori

doi:10.4161/hv.7.0.14571

Cited by 18 publications

(19 citation statements)

References 16 publications

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“…The prolongation of the survival was observed in the BCG-prime and HSP65 + IL-12/HVJ-booster group [27]. Improvement of ESR, increase of the body weight and augmentation of IFN- γ production, and proliferation of PBL were also observed in the BCG-prime and HSP65 + IL-12/HVJ-booster group.…”

Section: Resultsmentioning

confidence: 99%

Novel Prophylactic Vaccine Using a Prime-Boost Method and Hemagglutinating Virus of Japan-Envelope against Tuberculosis

Okada

Kita

Nakajima³

et al. 2011

Clinical and Developmental Immunology

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Objective. Mycobacterium tuberculosis infection is a major global threat to human health. The only tuberculosis (TB) vaccine currently available is bacillus Calmette-Guérin (BCG), although it has no efficacy in adults. Therefore, the development of a novel vaccine against TB for adults is desired. Method. A novel TB vaccine expressing mycobacterial heat shock protein 65 (HSP65) and interleukin-12 (IL-12) delivered by the hemagglutinating virus of Japan- (HVJ)- envelope was evaluated against TB infection in mice. Bacterial load reductions and histopathological assessments were used to determine efficacy. Results. Vaccination by BCG prime with IgHSP65+murine IL-12/HVJ-envelope boost resulted in significant protective efficacy (>10, 000-fold versus BCG alone) against TB infection in the lungs of mice. In addition to bacterial loads, significant protective efficacy was demonstrated by histopathological analysis of the lungs. Furthermore, the vaccine increased the number of T cells secreting IFN-γ. Conclusion. This vaccine showed extremely significant protection against TB in a mouse model, consistent with results from a similar paper on cynomolgus monkeys. The results suggest that further development of the vaccine for eventual testing in clinical trials may be warranted.

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Section: Resultsmentioning

confidence: 99%

Novel Prophylactic Vaccine Using a Prime-Boost Method and Hemagglutinating Virus of Japan-Envelope against Tuberculosis

Okada

Kita

Nakajima³

et al. 2011

Clinical and Developmental Immunology

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“…Rhesus macaques are the most commonly used species for testing TB vaccines, both historically (Barclay et al 1970;Ribi et al 1971;Janicki et al 1973) and recently (Langermans et al 2001;Sugawara et al 2009;Verreck et al 2009;Sharpe et al 2010;Rahman et al 2012), but cynomolgus macaques increasingly are being used (Langermans et al 2001;Okada et al 2009;Reed et al 2009;Kita et al 2011;Lin et al 2012b). In the sole direct comparison study, BCG vaccination provided better protection against high-dose M. tuberculosis challenge in cynomolgus compared with rhesus macaques (Langermans et al 2001), suggesting that rhesus were the preferred species in which to test whether a live vaccine candidate conferred better protection than BCG.…”

Section: Evaluating New Drugs and Vaccinesmentioning

confidence: 99%

“…Clinical assessment (body weight, hematological parameters, and CXR) has been used during the in-life challenge phase (Verreck et al 2009;Lin et al 2012b), but their predictive value has not been established. Postchallenge survival times of animals subjected to different vaccine regimens can be compared (Reed et al 2009;Sharpe et al 2010;Kita et al 2011;Lin et al 2012b). However, this poses both ethical concerns and statistical challenges, because genetic variability often results in large differences in survival times within experimental groups (Sharpe et al 2010).…”

Section: Evaluating New Drugs and Vaccinesmentioning

confidence: 99%

“…Some researchers homogenize whole lungs for plating (Langermans et al 2001;Verreck et al 2009), some use a stereologic approach to guide the selection of random tissue sections for plating (Luciw et al 2011), and some use a combination of lesion collection and random sampling (Lin et al 2009). Many researchers report bacterial burden as CFU/gram of tissue (Langermans et al 2001;Reed et al 2009;Verreck et al 2009) or CFU/ lung (Kita et al 2011). Lin et al devised a methodology to generate both a "CFU score" for quantitative analysis of bacterial burden and a calculable measure of bacterial dissemination (Lin et al 2009(Lin et al , 2012a.…”

Section: Evaluating New Drugs and Vaccinesmentioning

confidence: 99%

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Modeling Tuberculosis in Nonhuman Primates

Scanga

Flynn

2014

Cold Spring Harbor Perspectives in Medicine

134

117

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Nonhuman primates have emerged as an excellent model of human tuberculosis, in large part because they recapitulate the full spectrum of infection outcome and pathology seen in humans. Several variables inherent to the nonhuman primate models of tuberculosis are discussed in this review, including the monkey species, Mycobacterium tuberculosis strains, and routes of infection, all of which can influence the model to be chosen for various studies. New technologies for studying the microbiology, immunology, and pathogenesis of tuberculosis in nonhuman primates have greatly expanded the capabilities of this model for basic and translational studies, including the development and testing of new treatment and prevention strategies for tuberculosis.

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“…Both Ag85A and 85B have been shown to be among the most potent antigen species yet identified and are major targets of human T cell responses to M. tuberculosis and are leading components in vaccine candidates [9–12]. The various vaccine constructs expressing these antigens have been shown to afford levels of protection in mice, guinea pigs, and monkeys when administered by parenteral and aerosol routes[13, 14]. One particular vaccine candidate, a live recombinant modified vaccinia virus Ankara (MVA) expressing Ag85A (MVA85A) provided significant protection when administered following BCG vaccination in small vertebrate models [15].…”

Section: Introductionmentioning

confidence: 99%

Efficacy of parainfluenza virus 5 (PIV5)-based tuberculosis vaccines in mice

Chen

Gupta

et al. 2015

Vaccine

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Mycobacterium tuberculosis, the etiological agent of tuberculosis (TB), is an important human pathogen. Bacillus Calmette–Guérin (BCG), a live, attenuated variant of Mycobacterium bovis, is currently the only available TB vaccine despite its low efficacy against the infectious pulmonary form of the disease in adults. Thus, a more-effective TB vaccine is needed. Parainfluenza virus 5 (PIV5), a paramyxovirus, has several characteristics that make it an attractive vaccine vector. It is safe, inexpensive to produce, and has been previously shown to be efficacious as the backbone of vaccines for influenza, rabies, and respiratory syncytial virus. In this work, recombinant PIV5 expressing M. tuberculosis antigens 85A (PIV5-85A) and 85B (PIV5-85B) have been generated and their immunogenicity and protective efficacy evaluated in a mouse aerosol infection model. In a long-term protection study, a single dose of PIV5-85A was found to be most effective in reducing M. tuberculosis colony forming units (CFU) in lungs when compared to unvaccinated, whereas the BCG vaccinated animals had similar numbers of CFUs to unvaccinated animals. BCG-prime followed by a PIV5-85A or PIV5-85B boost produced better outcomes highlighted by close to three-log units lower lung CFUs compared to PBS. The results indicate that PIV5-based M. tuberculosis vaccines are promising candidates for further development.

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Development of therapeutic and prophylactic vaccine against Tuberculosis using monkey and transgenic mice models

Cited by 18 publications

References 16 publications

Novel Prophylactic Vaccine Using a Prime-Boost Method and Hemagglutinating Virus of Japan-Envelope against Tuberculosis

Novel Prophylactic Vaccine Using a Prime-Boost Method and Hemagglutinating Virus of Japan-Envelope against Tuberculosis

Modeling Tuberculosis in Nonhuman Primates

Efficacy of parainfluenza virus 5 (PIV5)-based tuberculosis vaccines in mice

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